Interferon-beta expressed by a rabies virus-based HIV-1 vaccine vector serves as a molecular adjuvant and decreases pathogenicity.
Type I interferon is important in anti-viral responses and in coordinating the innate immune response. Here we explore the use of interferon-beta to adjuvant the response to a rabies virus (RV) vaccine vector expressing both HIV-1 Gag and IFN-beta. Viral load and immune responses of immunized mice were analyzed over time. Our results indicate that the RV expressing IFN-beta (IFN+) is highly attenuated when compared to control RV and demonstrate that the expression of IFN-beta reduces viral replication approximately 100-fold. Despite the decrease in replication, those mice immunized with the IFN+ RV had a significantly greater number of activated CD8+ T cells. The increased activation of CD8+ T cells was dependent on IFN-beta signaling, as we saw no difference following infection of IFNAR-/- mice. Although mice immunized with IFN+ have a greater primary immune response than controls, immunized mice that were challenged with vaccinia-expressing Gag had no significant difference in the number or functionality of CD8+ T cells. The increased CD8+ T cell activation in the presence of IFN-beta, even with greatly reduced viral replication, indicates the beneficial effect of IFN-beta for the host.
Faul
Elizabeth J
EJ
Department of Microbiology and Immunology, Thomas Jefferson University, Philadelphia, PA, USA.
Wanjalla
Celestine N
CN
McGettigan
James P
JP
Schnell
Matthias J
MJ
D016915:AIDS Vaccines / Q000235:genetics* / Q000276:immunology*; D000276:Adjuvants, Immunologic / Q000235:genetics*; D000818:Animals; D000914:Antibodies, Viral / Q000096:biosynthesis; D000938:Antigen-Presenting Cells / Q000276:immunology; D001483:Base Sequence; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D017931:DNA Primers / Q000235:genetics; D015750:Genes, gag; D005822:Genetic Vectors; D015497:HIV-1 / Q000235:genetics* / Q000276:immunology* / Q000502:physiology; D007113:Immunity, Innate; D018928:Immunity, Mucosal; D007074:Immunoglobulin G / Q000096:biosynthesis; D007370:Interferon Type I / Q000235:genetics* / Q000276:immunology*; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D011820:Rabies virus / Q000235:genetics* / Q000276:immunology / Q000472:pathogenicity; D053633:Receptor, Interferon alpha-beta / Q000172:deficiency / Q000235:genetics; D011994:Recombinant Proteins; D011995:Recombination, Genetic; D015398:Signal Transduction; D014779:Virus Replication
D016915:AIDS Vaccines; D000276:Adjuvants, Immunologic; D000914:Antibodies, Viral; D017931:DNA Primers; D007074:Immunoglobulin G; D007370:Interferon Type I; D011994:Recombinant Proteins; D053633:Receptor, Interferon alpha-beta